Tag Archives: implants

Harvesting the heart’s kinetic energy to power implants

This work comes from Dartmouth College, an educational institution based on the US east coast in the state of New Hampshire. I hardly ever stumble across research from Dartmouth and I assume that’s because they usually focus their interests in areas that are not of direct interest to me,

Rendering of the two designs of the cardiac energy harvesting device. (Cover art by Patricio Sarzosa) Courtesy: Dartmouth College

For a change, we have a point of connection (harvesting biokinetic energy) according to a February 4, 2019 news item on ScienceDaily,

The heart’s motion is so powerful that it can recharge devices that save our lives, according to new research from Dartmouth College.

Using a dime-sized invention developed by engineers at the Thayer School of Engineering at Dartmouth, the kinetic energy of the heart can be converted into electricity to power a wide-range of implantable devices, according to the study funded by the National Institutes of Health.

A February 4, 2019 Dartmouth College news release, which originated the news item, describes the problem and the proposed solution,

Millions of people rely on pacemakers, defibrillators and other live-saving implantable devices powered by batteries that need to be replaced every five to 10 years. Those replacements require surgery which can be costly and create the possibility of complications and infections.

“We’re trying to solve the ultimate problem for any implantable biomedical device,” says Dartmouth engineering professor John X.J. Zhang, a lead researcher on the study his team completed alongside clinicians at the University of Texas in San Antonio. “How do you create an effective energy source so the device will do its job during the entire life span of the patient, without the need for surgery to replace the battery?”

“Of equal importance is that the device not interfere with the body’s function,” adds Dartmouth research associate Lin Dong, first author on the paper. “We knew it had to be biocompatible, lightweight, flexible, and low profile, so it not only fits into the current pacemaker structure but is also scalable for future multi-functionality.”

The team’s work proposes modifying pacemakers to harness the kinetic energy of the lead wire that’s attached to the heart, converting it into electricity to continually charge the batteries. The added material is a type of thin polymer piezoelectric film called “PVDF” and, when designed with porous structures — either an array of small buckle beams or a flexible cantilever — it can convert even small mechanical motion to electricity. An added benefit: the same modules could potentially be used as sensors to enable data collection for real-time monitoring of patients.

The results of the three-year study, completed by Dartmouth’s engineering researchers along with clinicians at UT Health San Antonio, were just published in the cover story for Advanced Materials Technologies.

The two remaining years of NIH funding plus time to finish the pre-clinical process and obtain regulatory approval puts a self-charging pacemaker approximately five years out from commercialization, according to Zhang

“We’ve completed the first round of animal studies with great results which will be published soon,” says Zhang. “There is already a lot of expressed interest from the major medical technology companies, and Andrew Closson, one of the study’s authors working with Lin Dong and an engineering PhD Innovation Program student at Dartmouth, is learning the business and technology transfer skills to be a cohort in moving forward with the entrepreneurial phase of this effort.”

Other key collaborators on the study include Dartmouth engineering professor Zi Chen, an expert on thin structure mechanics, and Dr. Marc Feldman, professor and clinical cardiologist at UT [University of Texas] Health San Antonio.

Here’s a citation and another link for the paper,

Energy Harvesting: Flexible Porous Piezoelectric Cantilever on a Pacemaker Lead for Compact Energy Harvesting by Lin Dong, Xiaomin Han, Zhe Xu, Andrew B. Closson, Yin Liu, Chunsheng Wen, Xi Liu, Gladys Patricia Escobar, Meagan Oglesby, Marc Feldman, Zi Chen, John X. J. Zhang. Adv. Mater. Technol. 1/2019 https://doi.org/10.1002/admt.201970002 First published: 08 January 2019

This paper is open access.

Controlling neurons with light: no batteries or wires needed

Caption: Wireless and battery-free implant with advanced control over targeted neuron groups. Credit: Philipp Gutruf

This January 2, 2019 news item on ScienceDaily describes the object seen in the above and describes the problem it’s designed to solve,

University of Arizona biomedical engineering professor Philipp Gutruf is first author on the paper Fully implantable, optoelectronic systems for battery-free, multimodal operation in neuroscience research, published in Nature Electronics.

Optogenetics is a biological technique that uses light to turn specific neuron groups in the brain on or off. For example, researchers might use optogenetic stimulation to restore movement in case of paralysis or, in the future, to turn off the areas of the brain or spine that cause pain, eliminating the need for — and the increasing dependence on — opioids and other painkillers.

“We’re making these tools to understand how different parts of the brain work,” Gutruf said. “The advantage with optogenetics is that you have cell specificity: You can target specific groups of neurons and investigate their function and relation in the context of the whole brain.”

In optogenetics, researchers load specific neurons with proteins called opsins, which convert light to electrical potentials that make up the function of a neuron. When a researcher shines light on an area of the brain, it activates only the opsin-loaded neurons.

The first iterations of optogenetics involved sending light to the brain through optical fibers, which meant that test subjects were physically tethered to a control station. Researchers went on to develop a battery-free technique using wireless electronics, which meant subjects could move freely.

But these devices still came with their own limitations — they were bulky and often attached visibly outside the skull, they didn’t allow for precise control of the light’s frequency or intensity, and they could only stimulate one area of the brain at a time.

A Dec. 21, 2018 University of Azrizona news release (published Jan. 2, 2019 on EurekAlert), which originated the news item, discusses the work in more detail,

“With this research, we went two to three steps further,” Gutruf said. “We were able to implement digital control over intensity and frequency of the light being emitted, and the devices are very miniaturized, so they can be implanted under the scalp. We can also independently stimulate multiple places in the brain of the same subject, which also wasn’t possible before.”

The ability to control the light’s intensity is critical because it allows researchers to control exactly how much of the brain the light is affecting — the brighter the light, the farther it will reach. In addition, controlling the light’s intensity means controlling the heat generated by the light sources, and avoiding the accidental activation of neurons that are activated by heat.

The wireless, battery-free implants are powered by external oscillating magnetic fields, and, despite their advanced capabilities, are not significantly larger or heavier than past versions. In addition, a new antenna design has eliminated a problem faced by past versions of optogenetic devices, in which the strength of the signal being transmitted to the device varied depending on the angle of the brain: A subject would turn its head and the signal would weaken.

“This system has two antennas in one enclosure, which we switch the signal back and forth very rapidly so we can power the implant at any orientation,” Gutruf said. “In the future, this technique could provide battery-free implants that provide uninterrupted stimulation without the need to remove or replace the device, resulting in less invasive procedures than current pacemaker or stimulation techniques.”

Devices are implanted with a simple surgical procedure similar to surgeries in which humans are fitted with neurostimulators, or “brain pacemakers.” They cause no adverse effects to subjects, and their functionality doesn’t degrade in the body over time. This could have implications for medical devices like pacemakers, which currently need to be replaced every five to 15 years.

The paper also demonstrated that animals implanted with these devices can be safely imaged with computer tomography, or CT, and magnetic resonance imaging, or MRI, which allow for advanced insights into clinically relevant parameters such as the state of bone and tissue and the placement of the device.

This image of a combined MRI (magnetic resonance image) and CT (computer tomography) scan bookends, more or less, the picture of the device which headed this piece,

Combined image analysis with MRI and CT results superimposed on a 3D rendering of the animal implanted with the programmable bilateral multi µ-ILED device. Courtesy: University of Arizona

Here’s a link to and a citation for the paper,

Fully implantable optoelectronic systems for battery-free, multimodal operation in neuroscience research by Philipp Gutruf, Vaishnavi Krishnamurthi, Abraham Vázquez-Guardado, Zhaoqian Xie, Anthony Banks, Chun-Ju Su, Yeshou Xu, Chad R. Haney, Emily A. Waters, Irawati Kandela, Siddharth R. Krishnan, Tyler Ray, John P. Leshock, Yonggang Huang, Debashis Chanda, & John A. Rogers. Nature Electronics volume 1, pages652–660 (2018) DOI: https://doi.org/10.1038/s41928-018-0175-0 Published 13 December 2018

This paper is behind a paywall.

Slip sliding away—making surfaces bacteria can’t grasp onto

Here’s another biomimicry story with a connection to Harvard University. From a Nov. 1, 2016 Beth Israel Deaconess Medical Center (Harvard Medical School Teaching Hospital) news release (also on EurekAlert),

Implanted medical devices like catheters, surgical mesh and dialysis systems are ideal surfaces on which bacteria can colonize and form hard-to-kill sheets called biofilms. Known as biofouling, this contamination of devices is responsible for more than half of the 1.7 million hospital-acquired infections in the United States each year.

In a report published in Biomaterials today, a team of scientists at Beth Israel Deaconess Medical Center (BIDMC), the Wyss Institute for Biologically Inspired Engineering and the John A. Paulson School of Engineering and Applied Sciences (SEAS) at Harvard University has demonstrated that an innovative, ultra-low adhesive coating prevented bacteria from attaching to surfaces treated with it, reducing bacterial adhesion by more than 98 percent in laboratory tests.

“Device related infections remain a significant problem in medicine, burdening society with millions of dollars in health care costs,” said Elliot Chaikof, MD, PhD, chair of the Roberta and Stephen R. Weiner Department of Surgery and Surgeon-in-Chief at BIDMC and an associate faculty member at the Wyss Institute. “Antibiotics alone will not solve this problem. We need to use new approaches to minimize the risk of infection, and this strategy is a very important step in that direction.”

The self-healing slippery surface coatings – known as ‘slippery liquid-infused porous surfaces’ (SLIPS) – were developed by Joanna Aizenberg, PhD, a Wyss Institute core faculty member, Professor of Chemistry and Chemical Biology and the Amy Smith Berylson Professor of Materials Science at SEAS at Harvard University. Inspired by the carnivorous Nepenthes pitcher plant that uses the slippery surface of its leaves to trap insects, Aizenberg engineered surface coatings that work to repel a variety of substances across a broad range of temperature, pressure and other environmental conditions. They are stable when exposed to UV light, and are low-cost and simple to manufacture. The current study is the first to demonstrate that SLIPS not only limit the ability of bacteria to adhere to surfaces, but also impede infection in an animal model.

SLIPS has been mentioned here before, most recently in a March 2, 2016 posting and before that in an Oct. 14, 2014 posting which appears to be precursor work for this latest research.

Getting back to the Nov. 1, 2016 news release, here’s more about plans for SLIPS and about recent trials,

“We are developing SLIPS recipes for a variety of medical applications by working with different medical-grade materials, ensuring the stability of the coating, and carefully pairing the non-fouling properties of the SLIPS materials to specific contaminates, environments and performance requirements,” said Aizenberg. “Here we have extended our repertoire and applied the SLIPS concept very convincingly to medical-grade lubricants, demonstrating its enormous potential in implanted devices prone to bacterial fouling and infection.”

In a series of trials, the researchers tested three SLIPS lubricants for their anti-adhesive qualities. First, they incubated disks of SLIPS-coated medical material ePTFE – a microporous form of Teflon – in a broth of Staphylococcus aureus (S. aureus), a generally harmless bacterium found in the nose and on skin, but one of the most common causes of hospital-acquired infections. After 48 hours, the three variations of SLIPS-treated disks demonstrated 98.3, 99.1 and 99.7 percent reductions in bacterial adhesion.

To test the material’s stability, the scientists performed the same experiment after soaking the SLIPS-coated samples for up to 21 days in a solution meant to simulate conditions inside a living mammal. After exposing these disks to S. aureus for 48 hours, the researchers found similar, nearly 100 percent reductions in bacterial adhesion.

Widely used clinically, medical mesh is particularly susceptible to bacterial infection. In another set of experiments to test the material’s biocompatibility, Chaikof and colleagues implanted small squares of SLIPS-treated mesh into murine models, injecting the site with S. aureus 24 hours later. Three days later, when the researchers removed the implanted mesh, they found little to no infection, compared with an infection rate of more than 90 percent among controls.

“Today, patients who receive implants often require antibiotics to keep the risk of bacterial infection at bay,” the authors wrote. “SLIPS coatings one day could obviate the widespread use of antibiotics and minimize the development of antibiotic resistant micro-organisms.”

“SLIPs have many promising medical applications that are in a very early stage of evaluation,” said Chaikof. “Clearly, there’s more work to be done before its introduction into the clinic, but this is one of a few studies that reinforces the exciting opportunities presented by this strategy to improve device performance and clinical outcomes.”

Here’s a link to and a citation for the paper,

An immobilized liquid interface prevents device associated bacterial infection in vivo by Jiaxuan Chen, Caitlin Howell, Carolyn A. Haller, Madhukar S. Patel, Perla Ayala, Katherine A. Moravec, Erbin Dai, Liying Liu, Irini Sotiri, Michael Aizenberg, Joanna Aizenberg, Elliot L. Chaikof. Biomaterials Volume 113, January 2017, Pages 80–92  http://dx.doi.org/10.1016/j.biomaterials.2016.09.028

This paper is behind a paywall.

Powering up your graphene implants so you don’t get fried in the process

A Sept. 23, 2016 news item on phys.org describes a way of making graphene-based medical implants safer,

In the future, our health may be monitored and maintained by tiny sensors and drug dispensers, deployed within the body and made from graphene—one of the strongest, lightest materials in the world. Graphene is composed of a single sheet of carbon atoms, linked together like razor-thin chicken wire, and its properties may be tuned in countless ways, making it a versatile material for tiny, next-generation implants.

But graphene is incredibly stiff, whereas biological tissue is soft. Because of this, any power applied to operate a graphene implant could precipitously heat up and fry surrounding cells.

Now, engineers from MIT [Massachusetts Institute of Technology] and Tsinghua University in Beijing have precisely simulated how electrical power may generate heat between a single layer of graphene and a simple cell membrane. While direct contact between the two layers inevitably overheats and kills the cell, the researchers found they could prevent this effect with a very thin, in-between layer of water.

A Sept. 23, 2016 MIT news release by Emily Chu, which originated the news item, provides more technical details,

By tuning the thickness of this intermediate water layer, the researchers could carefully control the amount of heat transferred between graphene and biological tissue. They also identified the critical power to apply to the graphene layer, without frying the cell membrane. …

Co-author Zhao Qin, a research scientist in MIT’s Department of Civil and Environmental Engineering (CEE), says the team’s simulations may help guide the development of graphene implants and their optimal power requirements.

“We’ve provided a lot of insight, like what’s the critical power we can accept that will not fry the cell,” Qin says. “But sometimes we might want to intentionally increase the temperature, because for some biomedical applications, we want to kill cells like cancer cells. This work can also be used as guidance [for those efforts.]”

Sandwich model

Typically, heat travels between two materials via vibrations in each material’s atoms. These atoms are always vibrating, at frequencies that depend on the properties of their materials. As a surface heats up, its atoms vibrate even more, causing collisions with other atoms and transferring heat in the process.

The researchers sought to accurately characterize the way heat travels, at the level of individual atoms, between graphene and biological tissue. To do this, they considered the simplest interface, comprising a small, 500-nanometer-square sheet of graphene and a simple cell membrane, separated by a thin layer of water.

“In the body, water is everywhere, and the outer surface of membranes will always like to interact with water, so you cannot totally remove it,” Qin says. “So we came up with a sandwich model for graphene, water, and membrane, that is a crystal clear system for seeing the thermal conductance between these two materials.”

Qin’s colleagues at Tsinghua University had previously developed a model to precisely simulate the interactions between atoms in graphene and water, using density functional theory — a computational modeling technique that considers the structure of an atom’s electrons in determining how that atom will interact with other atoms.

However, to apply this modeling technique to the group’s sandwich model, which comprised about half a million atoms, would have required an incredible amount of computational power. Instead, Qin and his colleagues used classical molecular dynamics — a mathematical technique based on a “force field” potential function, or a simplified version of the interactions between atoms — that enabled them to efficiently calculate interactions within larger atomic systems.

The researchers then built an atom-level sandwich model of graphene, water, and a cell membrane, based on the group’s simplified force field. They carried out molecular dynamics simulations in which they changed the amount of power applied to the graphene, as well as the thickness of the intermediate water layer, and observed the amount of heat that carried over from the graphene to the cell membrane.

Watery crystals

Because the stiffness of graphene and biological tissue is so different, Qin and his colleagues expected that heat would conduct rather poorly between the two materials, building up steeply in the graphene before flooding and overheating the cell membrane. However, the intermediate water layer helped dissipate this heat, easing its conduction and preventing a temperature spike in the cell membrane.

Looking more closely at the interactions within this interface, the researchers made a surprising discovery: Within the sandwich model, the water, pressed against graphene’s chicken-wire pattern, morphed into a similar crystal-like structure.

“Graphene’s lattice acts like a template to guide the water to form network structures,” Qin explains. “The water acts more like a solid material and makes the stiffness transition from graphene and membrane less abrupt. We think this helps heat to conduct from graphene to the membrane side.”

The group varied the thickness of the intermediate water layer in simulations, and found that a 1-nanometer-wide layer of water helped to dissipate heat very effectively. In terms of the power applied to the system, they calculated that about a megawatt of power per meter squared, applied in tiny, microsecond bursts, was the most power that could be applied to the interface without overheating the cell membrane.

Qin says going forward, implant designers can use the group’s model and simulations to determine the critical power requirements for graphene devices of different dimensions. As for how they might practically control the thickness of the intermediate water layer, he says graphene’s surface may be modified to attract a particular number of water molecules.

“I think graphene provides a very promising candidate for implantable devices,” Qin says. “Our calculations can provide knowledge for designing these devices in the future, for specific applications, like sensors, monitors, and other biomedical applications.”

This research was supported in part by the MIT International Science and Technology Initiative (MISTI): MIT-China Seed Fund, the National Natural Science Foundation of China, DARPA [US Defense Advanced Research Projects Agency], the Department of Defense (DoD) Office of Naval Research, the DoD Multidisciplinary Research Initiatives program, the MIT Energy Initiative, and the National Science Foundation.

Here’s a link to and a citation for the paper,

Intercalated water layers promote thermal dissipation at bio–nano interfaces by Yanlei Wang, Zhao Qin, Markus J. Buehler, & Zhiping Xu. Nature Communications 7, Article number: 12854 doi:10.1038/ncomms12854 Published 23 September 2016

This paper is open access.

‘Neural dust’ could lead to introduction of electroceuticals

In case anyone is wondering, the woman who’s manipulating a prosthetic arm so she can eat or a drink of coffee probably has a bulky implant/docking station in her head. Right now that bulky implant is the latest and greatest innovation for tetraplegics (aka, quadriplegics) as it frees, to some extent, people who’ve had no independent movement of any kind. By virtue of the juxtaposition of the footage of the woman with the ‘neural dust’ footage, they seem to be suggesting that neural dust might some day accomplish the same type of connection. At this point, hopes for the ‘neural dust’ are more modest.

An Aug. 3, 2016 news item on ScienceDaily announces the ‘neural dust’,

University of California, Berkeley engineers have built the first dust-sized, wireless sensors that can be implanted in the body, bringing closer the day when a Fitbit-like device could monitor internal nerves, muscles or organs in real time.

Because these batteryless sensors could also be used to stimulate nerves and muscles, the technology also opens the door to “electroceuticals” to treat disorders such as epilepsy or to stimulate the immune system or tamp down inflammation.

An Aug. 3, 2016 University of California at Berkeley news release (also on EurekAlert) by Robert Sanders, which originated the news item, explains further and describes the researchers’ hope that one day the neural dust could be used to control implants and prosthetics,

The so-called neural dust, which the team implanted in the muscles and peripheral nerves of rats, is unique in that ultrasound is used both to power and read out the measurements. Ultrasound technology is already well-developed for hospital use, and ultrasound vibrations can penetrate nearly anywhere in the body, unlike radio waves, the researchers say.

“I think the long-term prospects for neural dust are not only within nerves and the brain, but much broader,“ said Michel Maharbiz, an associate professor of electrical engineering and computer sciences and one of the study’s two main authors. “Having access to in-body telemetry has never been possible because there has been no way to put something supertiny superdeep. But now I can take a speck of nothing and park it next to a nerve or organ, your GI tract or a muscle, and read out the data.“

Maharbiz, neuroscientist Jose Carmena, a professor of electrical engineering and computer sciences and a member of the Helen Wills Neuroscience Institute, and their colleagues will report their findings in the August 3 [2016] issue of the journal Neuron.

The sensors, which the researchers have already shrunk to a 1 millimeter cube – about the size of a large grain of sand – contain a piezoelectric crystal that converts ultrasound vibrations from outside the body into electricity to power a tiny, on-board transistor that is in contact with a nerve or muscle fiber. A voltage spike in the fiber alters the circuit and the vibration of the crystal, which changes the echo detected by the ultrasound receiver, typically the same device that generates the vibrations. The slight change, called backscatter, allows them to determine the voltage.

Motes sprinkled thoughout the body

In their experiment, the UC Berkeley team powered up the passive sensors every 100 microseconds with six 540-nanosecond ultrasound pulses, which gave them a continual, real-time readout. They coated the first-generation motes – 3 millimeters long, 1 millimeter high and 4/5 millimeter thick – with surgical-grade epoxy, but they are currently building motes from biocompatible thin films which would potentially last in the body without degradation for a decade or more.

While the experiments so far have involved the peripheral nervous system and muscles, the neural dust motes could work equally well in the central nervous system and brain to control prosthetics, the researchers say. Today’s implantable electrodes degrade within 1 to 2 years, and all connect to wires that pass through holes in the skull. Wireless sensors – dozens to a hundred – could be sealed in, avoiding infection and unwanted movement of the electrodes.

“The original goal of the neural dust project was to imagine the next generation of brain-machine interfaces, and to make it a viable clinical technology,” said neuroscience graduate student Ryan Neely. “If a paraplegic wants to control a computer or a robotic arm, you would just implant this electrode in the brain and it would last essentially a lifetime.”

In a paper published online in 2013, the researchers estimated that they could shrink the sensors down to a cube 50 microns on a side – about 2 thousandths of an inch, or half the width of a human hair. At that size, the motes could nestle up to just a few nerve axons and continually record their electrical activity.

“The beauty is that now, the sensors are small enough to have a good application in the peripheral nervous system, for bladder control or appetite suppression, for example,“ Carmena said. “The technology is not really there yet to get to the 50-micron target size, which we would need for the brain and central nervous system. Once it’s clinically proven, however, neural dust will just replace wire electrodes. This time, once you close up the brain, you’re done.“

The team is working now to miniaturize the device further, find more biocompatible materials and improve the surface transceiver that sends and receives the ultrasounds, ideally using beam-steering technology to focus the sounds waves on individual motes. They are now building little backpacks for rats to hold the ultrasound transceiver that will record data from implanted motes.

They’re also working to expand the motes’ ability to detect non-electrical signals, such as oxygen or hormone levels.

“The vision is to implant these neural dust motes anywhere in the body, and have a patch over the implanted site send ultrasonic waves to wake up and receive necessary information from the motes for the desired therapy you want,” said Dongjin Seo, a graduate student in electrical engineering and computer sciences. “Eventually you would use multiple implants and one patch that would ping each implant individually, or all simultaneously.”

Ultrasound vs radio

Maharbiz and Carmena conceived of the idea of neural dust about five years ago, but attempts to power an implantable device and read out the data using radio waves were disappointing. Radio attenuates very quickly with distance in tissue, so communicating with devices deep in the body would be difficult without using potentially damaging high-intensity radiation.

Marharbiz hit on the idea of ultrasound, and in 2013 published a paper with Carmena, Seo and their colleagues describing how such a system might work. “Our first study demonstrated that the fundamental physics of ultrasound allowed for very, very small implants that could record and communicate neural data,” said Maharbiz. He and his students have now created that system.

“Ultrasound is much more efficient when you are targeting devices that are on the millimeter scale or smaller and that are embedded deep in the body,” Seo said. “You can get a lot of power into it and a lot more efficient transfer of energy and communication when using ultrasound as opposed to electromagnetic waves, which has been the go-to method for wirelessly transmitting power to miniature implants”

“Now that you have a reliable, minimally invasive neural pickup in your body, the technology could become the driver for a whole gamut of applications, things that today don’t even exist,“ Carmena said.

Here’s a link to and a citation for the team’s latest paper,

Wireless Recording in the Peripheral Nervous System with Ultrasonic Neural Dust by Dongjin Seo, Ryan M. Neely, Konlin Shen, Utkarsh Singhal, Elad Alon, Jan M. Rabaey, Jose M. Carmena. and Michel M. Maharbiz. Neuron Volume 91, Issue 3, p529–539, 3 August 2016 DOI: http://dx.doi.org/10.1016/j.neuron.2016.06.034

This paper appears to be open access.

Biocompatible cellulose sheaths for implants

Strictly speaking this is not my usual scale which is nano but the topic is of some interest to me so here goes a micro scale story.

It’s well known the body rejects foreign objects no matter how helpful or necessary to our continued existence. A Jan. 19, 2015 news item on Nanowerk describes research into developing more biocompatible implants (Note: A link has been removed),

The human immune system distinguishes between endogenous and foreign bodies. This is highly useful when defending the body against pathogens, but can become a problem if a patient requires an artificial implant like a pacemaker or a heart assist device. In some cases the body responds with an inflammation, and it may even reject the device altogether. Researchers at ETH Zurich [Swiss Federal Institute of Technology] are now introducing a promising method to ameliorate this process –fabricating pre-structured cellulose materials that cover or coat devices with three-dimensional micro-structures and thus make them exceptionally biocompatible (“Surface-Structured Bacterial Cellulose with Guided Assembly-Based Biolithography (GAB)”).

A Jan. 19, 2015 ETH Zurich press written by Angelika Jacobs, which originated the news item, describes the research in more detail,

Researchers had already discovered that cells interact better with rough or structured surfaces than with smooth ones and can cling to them more effectively. However, until now it has not been possible to apply these surface structures to one of the most promising materials in the field of medicine: cellulose produced by bacteria. Bacterial cellulose has received major attention in research in recent years due to the fact that it is durable, adaptable and well tolerated by the human body. For example, practical tests are already being carried out on artificial blood vessels and cartilage made using bacterial cellulose. The versatile material is also an effective option for use as wound dressings.

A research team led by ETH Professor Dimos Poulikakos and Aldo Ferrari at the Laboratory of Thermodynamics in Emerging Technologies, has now succeeded in creating bacterial cellulose with a controlled surface structure. This is produced using a silicon mould with a three-dimensional, optimised geometry (such as a line grid) on a micrometre scale, which is then floated on the surface of a nutrient solution in which the cellulose-producing bacteria grow. The bacteria create a dense network of cellulose strands at the interface between liquid and air. The researchers observed that when the mould was present the bacteria conformed to it, producing a cellulose layer together with a negative replica of the line grid.

Surface structure conveys signals to cells

The line grid also enabled the bacteria to produce an increased number of cellulose strands in approximate alignment with the grid. “In principle, human cells have the ability to identify fibres, such as endogenous collagen, as part of the connective tissue,” explains Aldo Ferrari. The cellulose strands and the grid pattern provide cells with an orientation along predetermined paths that they can sense. “This is of major benefit to wound dressings. Skin cells could grow over a wound more effectively if they moved in accordance with structured cellulose.” The material also has a sort of memory: the structure is even retained when the cellulose is dried for storage purposes and moistened again just before use.

Poulikakos explains that in the production of cellulose surfaces, it is now possible to provide them with a message for the cells that will grow there in the future. “Think of it as a form of Braille.” This enables the right ‘message’ intended for later use to be written on the surface.

Less inflammation due to a structured surface

Such structures serve not only as means of orientation for cells, but also help to minimise the body’s rejection reaction to an artificial implant. In studies using mice, researchers compared smooth and structured cellulose and discovered that the mice with structured cellulose inserted under their skin showed significantly fewer signs of inflammation.

The researchers are now looking to follow up on these initial promising results by testing the material under more complex conditions. They could, for example, structure the cellulose surface of artificial blood vessels in a way that optimises the flow of blood, thereby ensuring that these vessels do not become blocked as easily.

As is often the case these days, there the researchers will be attempting to commercialize this work (from the news release; Note: A link has been removed),

In addition, researchers working with Poulikakos and Ferrari have founded the spin-off Hylomorph to make the method market-ready. “We are planning to apply the structured cellulose as part of the “Zurich Heart” project at the new Wyss Translational Center [founded jointly by ETH Zurich and the University of Zurich; it is not related to the Wyss Institute of Biologically Inspired Engineering at Harvard University],” reveals Poulikakos. The aim of this project is to develop artificial cardiac pump devices that help patients with serious heart problems in the period before a heart donor becomes available – they could even be used as a permanent alternative to a donor heart. Although cardiac pumps are already available, the options that they provide have been limited until now as they are not particularly durable and can cause complications. “Our aim is for artificial implants to be accepted by the patient’s body without inflammation or rejection,” explains Ferrari. As part of the Zurich Heart project, the researchers are, in effect, helping to design the packaging and internal coating for the optimised cardiac pumps. The aim is to minimise the number of complications in the future.

Here’s a link to and a citation for the paper,

Surface-Structured Bacterial Cellulose with Guided Assembly-Based Biolithography (GAB) by Simone Bottan, Francesco Robotti, Prageeth Jayathissa, Alicia Hegglin, Nicolas Bahamonde, José A. Heredia-Guerrero, Ilker S. Bayer, Alice Scarpellini, Hannes Merker, Nicole Lindenblatt, Dimos Poulikakos, and Aldo Ferrari. ACS Nano, Article ASAP DOI: 10.1021/nn5036125
Publication Date (Web): December 19, 2014

Copyright © 2014 American Chemical Society

The paper is behind a paywall.

I can’t find a Hylomorph website or one for the Wyss Translational Center (there is a Dec. 12, 2014 ETH media release announcing its existence).

Monitoring hip and knee replacements from inside

I have a fondness for the ‘My mother is a cyborg‘ posting that I wrote for April 20, 2012 largely due to the title which amuses and makes the piece easy to find. In common with this posting, ‘My mother …’ is about  replacements (hip, etc.) and nanotechnology.

Before spilling the latest news, here’s the reason for all the research interest in hip replacements, from my April 20, 2012 posting,

Since her [my mother’s] operation, I’ve become somewhat interested in hip replacements. From the April 19, 2012 news item by Anne Trafton on Nanowerk about research at MIT (Massachusetts Institute of Technology),

Every year, more than a million Americans receive an artificial hip or knee prosthesis. Such implants are designed to last many years, but in about 17 percent of patients who receive a total joint replacement, the implant eventually loosens and has to be replaced early, which can cause dangerous complications for elderly patients.

To help minimize these burdensome operations, a team of MIT chemical engineers has developed a new coating for implants that could help them better adhere to the patient’s bone, preventing premature failure.

There’s a researcher at Case Western Reserve University (Ohio) who is taking a different approach (from the MIT team) by utilizing an emergent process, magnetic particle imaging, according to the Feb. 5, 2013 news item on Nanowerk,

A Case Western Reserve University chemistry professor has begun imbedding magnetic nanoparticles in the toughest of plastics to understand why more than 40,000 Americans must replace their knee and hip replacements annually.

Anna C. Samia, an assistant professor who specializes in metallic nanostructures, has been awarded a five-year $600,000 National Science Foundation-CAREER grant to create new materials and equipment to test ultra-high molecular weight polyethylene used to make artificial joints. She and her team of researchers will also develop magnetic particle imaging techniques to monitor degradation and wear.

The US National Science Foundation gives more information about Samia’s project on her ‘Magnetic Imaging Guided Composite Materials Development’ Career Award webpage including this non-technical summary I’ve excerpted,

Polyethylene is widely used as a component in the fabrication of joint prostheses. A major downside of this material is that it can undergo excessive wear leading to premature loosening of the implant, which in turn can lead to failure and complicated replacement revision surgeries. Studies have shown that polyethylene wear in artificial joint replacements are not always identical and are not easily explained by exclusively mechanical factors. In cases of premature and excessive wear of polyethylene bearings, chemical degradation and oxidation of the polymer can significantly lower its mechanical resistance and result in an accelerated wear-off process. While ex vivo studies have been conducted on previously used polyethylene acetabular cups to understand the factors contributing to implant failure, the degradation mechanism is still not completely understood. An improved assessment of the structural integrity of the polyethylene material used in implants as subjected to mechanical and chemical stress will provide valuable information on the material’s durability, and can help predict its wear and degradation over time. To study the real-time degradation of implant materials in various chemical and biological fluid environments, the proposed project aims to develop new polyethylene composite materials that can be investigated using an emerging imaging modality called magnetic particle imaging (MPI). The proposed research will transform the wear debris monitoring of polyethylene implant materials and impact annually one million people in the U.S. alone who undergo hip and knee replacement surgeries. The educational impact of this project will build on current initiatives to educate high school, undergraduate and graduate students through the development of cross-disciplinary courses and hands-on research programs that will incorporate the interplay between materials fabrication and imaging tools. Moreover, a modular “Traveling Magnetism Show” will be developed for K-12 students at four adaptive levels and will be showcased in local schools and science museums. In addition, a new “Women in Chemistry Workshop Series at CWRU” will be established to provide a mentoring and training platform for graduate and post-graduate female chemistry students. [emphasis mine] This program will facilitate monthly discussions and workshops to tackle important aspects of career advancement specific to women scientists.

Future applications are also being considered according to the news item on Nanowerk,

Beyond artificial knees and hips, Samia said the nanoparticles, methods and technologies developed in this study would also be useful for learning how stents, electrodes, artificial organs and other implants degrade inside the body.

“A lot of other materials are used for implants,” she said. “It will be interesting to study them over time.”

As per my emphasis earlier, it’s intriguing to note that Samia’s grant is also being applied to outreach and support programs for female chemistry students.